Hormone Disruptors
- Synthetic chemicals
- >100,000 produced within the last 50 years
- global dispersion throughout the biosphere
- evidence that some interfere with hormone functions
- pesticides (e.g., DDT)
- substances in consumer products (e.g., bisphenol A)
- by-products of industrial processes & incineration
(e.g., PAH)
- xenoestrogens (synthetic estrogens)
Case Study: Alligators in Lake Apopka, Florida
- Initial concerns
- chemical plant spill of dicofol (pesticide with ~ 15% DDT) in
1980
- reproductive failure compared to alligators in other lakes
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hatchlings
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Lake Apopka
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20% *
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5 adjacent lakes
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70%
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* 50% mortaility within 2 weeks
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Reproductive failure associated with elevated levels of DDE (DDT
breakdown)
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DDE concentration
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Lake Apopka water
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ND (nondetected)
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alligator eggs
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6 ppm
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Biochemical analyses of alligator hatchlings from Lake Apopka
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males
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- elevated levels of estrogen
- depressed levels of testosterone
- abnormal seminal vesicles
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females
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- "super estrogenized"
- ovaries with abnormal eggs
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- Laboratory studies (using alligator eggs from a control site)
- painted with estradiol or DDE
- incubated at high temperatures (where only males are formed)
- incubated at low temperatures (where females are formed)
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estradiol treated eggs
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only females
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DDE treated eggs
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40% male
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20% female
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40% intersex
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estrogen:testosterone ratios Lake Apopka
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- Initial field study at Lake Apopka (1994)
- "seriously reduced penises" (1/4 - _normal size) of alligators
- females appeared to be "sexually incompetent"
- Subsequent studies
- feminized alligators are not suffering from an excess of
estrogen-like compounds
- DDE blocks androgen effects "emasculated" alligators
- there are no known xenoandrogens, but there are environmental
anti-androgens
Other Reported or Suspected Effects of Xenoestrogens
- DDT in avian endocrine systems
- avian egg shell thinning
- brown pelican (California)
- double crested cormorant (California)
- bald eagles (Great lakes)
- skewed sex ratios
- Western gulls (Santa Barbara I., California)
- feminization of male chicks (laboratory study)
- California and Western gulls developed oviducts
- PCB in avian endocrine systems
- incompletely developed female reproductive organs
- (New Bedford Harbor, MA near a PCB toxic waste site)
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Contaminants (nonyl and octylphenols) in wastewater effluents
(from surfactants)
- increased production of vitellogin (precursor of egg yolk)
- normally ~ absent in male fish
- produced in male fish exposed to estrogen (100,000 x normal
concentration)
- found in male rainbow trout in English rivers (28 locations)
Terminology
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andro:
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male
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androgen (any substance, natural or synthetic, that
promotes masculimity)
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estrus:
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female reproductive cycle
estrogen (female hormone)
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xeno:
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alien, strange, foreign
xenoestrogens (synthetic estrogens)
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Estrogens:
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Biological Functions
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adult female
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- prepares uterus to accept eggs
- pregnancy and lactation
- lowers risk of heart attack & osteoporosis
- stimulates growth of breast & uterine cancer
- other roles ?
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adult male
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- manufactured in testicles
- found in sperm
- too much inhibits sperm production & growth of
testes
- other roles ?
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- prenatal and postnatal development of males and females
- specific ratio of estrogen to androgen
- sexual differentiation
- formation of reproductive organs
-
estrogen's biological functions
- activated by binding to its hormone receptor
- estrogen receptor is "promiscuous" (binds with other
compounds)
Disruption of the Hormone System
mimics: initiate same hormonal response
stimulators: stimulate formation of additional hormone receptors
blockers: occupy a receptor site
hormone flushers: deplete hormone level by accelerating breakdown
enzyme flushers: increase hormone level by depleting deactivating
enzymes
destructors: alter or destroy hormones
Case Study in Humans : DES
- DES (diethylstilbestrol)
- synthetic estrogen used to prevent miscarriages (1948-1971)
- 2 to 6 million women treated in the US and Europe
- no adverse effects in treated women
- used as a growth promoter in cattle
- 27,000 administered to catle
-
- Environmental consequences
- 0.1% DES daughters developed a previously rare cancer
- DES sons have a higher rate of testicular cancer
- DES sons and daughters have a higher incidence of
abnormalities
- reproductive tract
Toxic Effects of Synthetic Hormone Disruptors
1. Decreased Immune Functions
- DES offspring with an increased prevalence of:
- relatively rare immunologic hyperactivity
- rheumatic fever
- microbial infection (Streptocci)
- Marine mammal die-offs from infection associated with
xenoestrogens (PCB, dioxin)
- seals in the North Sea (1989)
- seals in the Baltic Sea (1992)
- dolphins along the US east coast (1989)
- stripped dolphins in the Mediterranean Sea (1994)
- Variations in immunity among Inuit corresponds with PCB levels
- respiratory and ear infections of PCB contaminated population
15 x control
- PCB in Inuit breast milk ~ 7 to 10 x control
2. Reproductive Effects
- Reproductive abnormalities:
- changes in uterus, damage to the oviduct, maldescent or
damage to the testes
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- DES offspring
- daughters
- greater difficulty in conceiving
- increased miscarriages
- increased spontaneous abortions
- 3-5 x more tubal pregnancies
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- sons
- higher incidence of malformed or abnormally small penis
- higher incidence of undescended testicles at birth
- malformed or abnormal sperm
- genital-tract abnormalities that may cause sterility
- reproductive failure in contaminated fish
- pallid sturgeon in the Missouri & Mississippi rivers
- 10 years with no recorded reproduction in fish
- high PCB and DDT measured in fish
- for the last 15 years the gonads, reportedly:
- "aren't distinctly male of female anymore"
- salmon in the Great lakes
- need to be sustained by stocking programs
- 100% thyroid enlargement (up 1 million x normal size)
- most of the salmon have hermaphroditic reproductive
systems
- reproductive failure in beluga whales in the Gulf of St.
Lawrence
- reproduction rates at 30-40% those of controls (Arctic)
- mammary gland lesions in 36% of females biopsied
- first reported case of true hermaphroditism in a cetacean
anywhere
- 2 testicles, 2 separate ovaries, complete ducts of each sex
- reproductive failure in Florida panthers
- 67% of males born with cryptorchidism: undescended testicle(s)
- between 1985 and 1990, compared to only 14% a decade earlier
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- Decreased sperm count and motility
- SEE: November 1997 Environmental Health Perspectives
meta-analysis
3. Cancers and Cell Proliferation of Reproductive
Organs
- Many tumors are estrogen dependent
- excess exposure to estrogen increases the risk of :
- breast cancer
- endometrial cancer (uterus)
- endometriosis (cells growing outside the uterine wall)
- estimated to afflict 10-20% women of childbearing age
(US)
- testicular cancer ?
SEE: New England Journal of Medicine, October, 1997
4. Behavioral, Neurological and Cognitive Effects
- Laboratory studies have shown in utero exposure to
xenoestrogens affects:
- sexual behavior
- aggression
- neurological response
- learning ability
- ex. roosters
- never crowed, strutted, or exhibited mating behavior
- ex. rats
- continuous "spinning syndrome"
- depressed reflexes and learning deficits
- ex. rhesus monkeys
- motor impairment, memory and learning deficits
- hyperactivity
- References:
- NEJM (class refs)
- Environmental Health Perspectives (class refs)
- Chemical & Engineering News (class ref)
much of the information for this section was taken from the World Wildlife
Federation Web site <http://www.wwf.ca/satellite/hormone-disruptors>
